1. Field of the Invention
The present invention relates to a method of evaluating prostatic disease including at least one of prostatic cancer and prostatic hypertrophy, which utilizes a concentration of an amino acid in blood (plasma).
2. Description of the Related Art
Prostatic cancer has the rate of a predictive value of the number of deaths from cancer by organ is 3.90 in 2015 as compared with in 1990, which is the highest rate of all cancers. Therefore, to reduce increase in future death rate, it need to be diagnosed with high precision in an early stage.
At present, the diagnosis of prostatic cancer is performed by prostate-specific antigen (PSA), rectal examination, and transrectal ultrasonography. An abnormal case is subjected to prostate six sextant biopsies by transrectal ultrasonic guide for definitive diagnosis.
However, PSA, which occurs, not only in prostatic cancer tissue, but also in prostatic hypertrophy tissue, is difficult to discriminate between prostatic cancer in an early stage and prostatic hypertrophy, with the biopsy positive predictive value being as low as 3% to 4%. In addition, rectal examination and transrectal ultrasonography have lower sensitivity and biopsy positive predictive value than PSA. Further, prostate six sextant biopsies by transrectal ultrasonic guide, which is definitive diagnosis, is a high-invasiveness examination so that it is not realistic to subject all patients who are suspected of having prostatic cancer to it. Therefore, from the viewpoint of the physical load on patients and the cost effectiveness, desirably, subjects having a high possibility of occurrence of prostatic cancer are selected by a method with less invasiveness and mental pain, the selected subjects are diagnosed, and the subjects who have obtained definitive diagnosis are to be treated.
It is known that blood amino acid concentration is changed by occurrence of cancer. For instance, Cynober (see “Cynober, L. ed., Metabolic and therapeutic aspects of amino acids in clinical nutrition. 2nd ed., CRC Press.”) has reported that the consumption amount in cancer cells of each of glutamine mainly as an oxidative energy source, arginine as the precursor of nitrogen oxide or polyamine, and methionine subjected to activation of methionine take-in ability by cancer cells is increased. In addition, Vissers et al. (see “Vissers, Y. L J., et. al., Plasma arginine concentration are reduced in cancer patients: evidence for arginine deficiency?, The American Journal of Clinical Nutrition, 2005 81, p. 1142-1146”), Kubota (see “Kubota, A., Meguid, M. M., and Hitch, D. C., Amino acid profiles correlate diagnostically with organ site in three kinds of malignant tumors., Cancer, 1991, 69, p 2343-2348”), Park (see “Park, K. G., et al., Arginine metabolism in benign and malignant disease of breast and colon: evidence for possible inhibition of tumor-infiltrating macrophages., Nutrition, 1991 7, p. 185-188”), Proenza et al. (see “Proenza, A. M., J. Oliver, A. Palou and P. Roca, Breast and lung cancer are associated with a decrease in blood cell amino acid content. J Nutr Biochem, 2003. 14(3): p. 133-8”), and Cascino (see “Cascino, A., M. Muscaritoli, C. Cangiano, L. Conversano, A. Laviano, S. Ariemma, M. M. Meguid and F. Rossi Fanelli, Plasma amino acid imbalance in patients with lung and breast cancer. Anticancer Res, 1995. 15(2): p. 507-10”) have reported that the plasma amino acid composition of cancer patients is different from that of healthy subjects.
WO 2004/052191 and WO 2006/098192 disclose a method for associating amino acid concentration with biological state. WO 2008/016111 discloses a method for evaluating the state of lung cancer using an amino acid concentration.
However, there is a problem that diagnosing methods and apparatuses, which use a plurality of amino acids as explanatory variables to diagnose the presence or absence of occurrence of prostatic cancer, prostatic hypertrophy, and other prostatic diseases, have not developed from the viewpoint of time and cost, and have not been practically used. In addition, there is a problem that even when the presence or absence of occurrence of prostatic cancer, prostatic hypertrophy, and other prostatic diseases is discriminated by an index formula group for discriminating lung cancer disclosed in WO 2008/016111, sufficient discriminative ability cannot be obtained due to different discriminated targets.